Left ventricular (LV) output increases markedly from fetal to neonatal life. By applying new techniques to the study of the fetus and the neonate, this proposal will test specific hypotheses that clarify the bases of this increase. 1) The Frank-Starling relationship is an important factor in the function of the immature LV. 2) With birth LV end-diastolic volume (LVEDV) increases, enhancing LV stroke volume (SV). 3) The neonatal fall in right ventricular (RV) volume and systolic pressure allow, through ventricular interaction, greater LV filling and ejection for comparable filling pressures. 4) With birth inotropy in increased, in part, through sympathetic stimulation. The chronic instrumentation of the fetal lambs (124-130 days of gestation) includes: an ascending aorta electromagnetic flow probe, ventricular dimension transducers and catheters, LV micromanometer pressure transducer, tracheal catheter, vena caval and pulmonary artery occluders, and atrial pacing electrodes. Three LV dimensions will be used to derive in-vivo EDV, using a prolate ellipsoid model. In-vitro calibration will provide correction factors for the in-vivovivo data. The lambs will be studied in utero and as neonates and the data will be compared. Blood infusions, transient vena caval obstruction, and right atrial and left atrial pacing will be used to obtain the LVEDV-LVEDP and LVSV-LVEDV relationships at different RV end-diastolic dimensions. The effects of RV afterload on the relationships between LVEDV-LVEDP, LVSV-LVEDV, and LV (dP/dt)max-LVEDV will examined by transient constrictions of the main pulmonary artery and by decreasing the inspired oxygen content of the neonate. LV inotropy will be examined with the end-systolic pressure-volume relationship (EES) and post- extrasystolic potentiation (PESP). The effects of preload, inotropy, afterload and heart rate on EES will be established for the fetus. The EES, PESP, and LV output of the fetus and neonate will be compared and the effects of sympathetic blockade examined. Through the application of new techniques to the fetus and neonate, the proposed studies will provide new data upon which it will be possible to formulate the relationships that give rise to the increase in cardiac output following birth. The effects of perinatal diseases on the heart make this information of fundamental importance in the care of the in-utero and newborn infant.